Process for the manufacture of certain para-n-sec-alkylamino-phenols and other substituted phenols and their salts



Patented May 7, r

--2,000,034i. r a V PROCESS FOR .THEIMANUFACTURE onenej QTAIN PARAj-N-SEC-ALKYLAMINOI-PHEQ-- I 29, 1925, by the interaction NOLS AND "OTHER SUBSTITUTED PHE- NOLS AND 'THEIR SALTS A Randolph TMajor, Westfield, 'as signorto f Merck .& Co..Inc., Rahway, N. .l., a corporation of New,,Jersey -No Drawing. 'Application July30, 1931,; Serial No. 554,075-

v v I 8 Claims. (c1. zea -lee) i Y This invention relates to improved processes by the catalytic reduction-at room temperature oi;

a. mixture of aniline and cyclohexanone in the presence of a platinum catalyst. Y

Riedel, A. (1%., German Patent 423,132, March 4, 1924, has described the preparation'ofaralkylarylamines by the catalytic reductionoi N-arylaldimines- Skita and Keil, Berichte, 613, 1458, 1682 (1928) have described thepreparation of alkylsec-alkylamines by the catalytic reduction of mixtures of ketones and alkylamines in various solvents in the presence of a platinum catalyst. Major, J. Am; Chem. Soc., 53, 1901 .(1931), has shown that para-N-sec-alkylamino+phenols may be prepared by the catalytic reduction at room temperature of a mixture of p-nitro-br nitrosophenol and a ketone in. the presence of. a platinum catalyst. On the other hand, it has been shown that there is no appreciable reaction at room temperature between p-aminopheriol, acetone, and hydrogen'in the presence of a platinum catalyst. Y

I have also found that the preparation of para- N-sec-alkylamino-phenols may also conveniently and relatively cheaply be obtained very pure form by the reduction of j p-(isoalkylideneamino) -phenols, R(R')C:NC6H4OH, in an inert solvent by hydrogen at room temperature in the presence of a metallic catalyst, preferably platirim or 1 palladium, which appear to be most serviceable for the purpose when working at such temperatures. I have also found that para-N- sec-alkylamino-phenols may, also, conveniently be prepared by reducinga solution of p -aminophenol in an aliphatic ketone by hydrogen in the presence of a metallic catalyst such as platinum or palladium at or near the boilingpoint of the ketone. Presumably, the ketone first condenses with the p-aminophenolto' form p- (isoalkylidenee amino),phenolwhich in 'turnis reduced to th para-'N-sec-alkylamino-phenol. Inthe process thus carried out with paraaminophenol some of thelatter remains at'the v end of the reaction. and appears as an impurity which can, however, be readily removed 'from the N-alkylamino phenol by combining the aminophenol with aldehydes' according to known methods. "A- convenient method: for accomplishing the separation of the aminophenol is? as follows: Y I An. aqueous solution ofthemixture of the palkylamino-phcnol'and the p-aminophenol in a weak acid is shaken -wlth -an aromatic aldehyde. The condensationprcduct between the aldehyde and the 'p-aminophenol 'isremoved. Excess of the aldehyde is removed by" heat or an inert solvent. The remaining solution contains the salt of the purified p-alkylamino-phenol. The free'base may be obtained-by means o'f alkalies.

' These 'isoalkylarnino phenols after purification may readilybeiconverted into soluble-salts, for example the sulphate or hydrochloride. The salts of p isoalkylamino-phenols are white, crystalline compounds;readilysoluble in Water and are highlydesirable for use as photographic developers and for hair dyes.

, The followi'ng examples will illustrate preferred methods of applying my invention:

Example-1. 2.5 grams: of p-(isopropylideneamino) -phenol is: dissolved inalcohol at room temperature; To this solution is then' added 0.1

gram of a platinum oxide catalyst prepared preierably=according to the niethcdof Adams and Shriner, J. Am; Chem. Soc.', 45, 217111923). The '0 mixture" is shaken in an atmosphere of hydrogen at room temperature until-the calculated amount of hydrogen has been absorbed. Afterthe catalysth'asbeen filtered off, the residue of alcohol is distilled off in vacuo. The remaining solid is recrystallizedfrom benzene. It is obtained in the form oflwhite, needle-like crystals, soluble in dilute acids and alkaliesfand in ether and in alcohol, and insoluble in water. and hasa meltingv point of l-l56 C.

In the place of alcohol, obviously suitable inert solvent, such as, forinstance, dioxane or acetone, may be used as asolvent for the p-(isov propylidene-amino) phenol. l

Example II.-l3.9 grams, of p-aminophenol is dissolved in an excess'of acetoneat'room temperature. To this solution is then added 0.1 gram of a platinum oxide catalyst, prepared preferably according to the method above described.

The mixture is first heated to the boiling point and then shaken in an atmosphere of hydrogen until the calculated amount of hydrogen has been absorbed. After the catalyst, has been filtered off, the residue of acetone is distilled off in 'vacuo,

The remaining material is then dissolved in dilute acetic-acid. IMore than suflicient benzalde- The mixture.- is vigorously shaken for half an hour. .Itis. then extracted with ether. Thef aqueo'usjlayer is made neutral with sodium carbonate. The p- 7 isopropyl-aminophenol which precipitates out is filtered off, and recrystallized from benzene. It

I is obtained in the form of white',' needle-likecrystals, soluble in dilute acids and alkalies, and in ether and in alcohol, and insoluble in water, and has a meltingpoint of 155- 15 6 -.-C. :'1 7

These exemplifications are given by way of illustration, but it is obvious that some. qualitative and quantitative changes may be madef'in the details of processes, without departing from spirit and scope of my invention. 1 A

. Thus, in Example I,a s already explained, any appropriate inert solvent will serve, in placeqof the alcohol as exemplified; .also, any Suitable catalyst such as. palladium may replace the platinum as described. As explainedglaten'a nickel catalyst will also serve, if working at highe er temperature, for instance, and other similar adaptations will readily suggest themselves for the production of the specific compounds to which theqprocess may. be. directed. In ,Example II the method of, removing the remaining para amino-phenol is-illustrated with-the use of benzaldehyde, but it. willtalso be obvious that other suitable aromatic .aldehydes will serveas.

equivalents for this purpose, and throughout any suitable recrystalizing medium may be used as penol and p-amino-phenol, respectively, but I find that the processasapplied may be employed generally also. for the preparation of homologous secondary alkylamino-phenols, by treating the 7 corresponding p-(sec alkylidene amino) -phenol by the method of Example L1. or, dissolving ;the

' p-amino. phenol in the, appropriate ketone, an-

alogously as in Example II. aI.- have.also. found thatI am not limited to these precise forms of ma-' terials but may use quitesatisfactoriiy in their 'placessuitable carbon. substituted derivatives. 'It

' is also possible .to carry out and'expedite these reactions somewhat by working at highe'r temperatures and under increased atmospheric pres.-. sures. with appropriately modified conditions. At

of thetendency to theformation of dialkyl com-' pounds. I have found, on. the whole, that working at room temperatures and at normal pressure, and with the catalysts," as set forth in the examples, yields the most. satisfactory average practical resultsas to purity and yields.

Having thus set forth the manner and means ofcarrying. out' this invention, I request the issuance of Letters Patent on the following claims: 1. In a process of making para-N-sec-alkylamino-phenols, the step of reducing p-(isoalkylidene amino) phenols, in alcoholic solution, by hydrogen with the aid of a platinum catalyst.

2. In .a process of making .para-N-sec-alkylamino-phenols, the step of reducing p-(isoalkylidene amino) -phenols, in solution in an inert "*solvent, byhydrogen with the aid of a metal hydrogenation catalyst. 3 ,,The process" of making para-N-sec-alkylamino-phenols comprising the solution of p-(isov alkylideneamino) -phenol in an inert solvent, adding a metal hydrogenation catalyst, shaking the mixture inan atmosphere of hydrogen until the required amount of hydrogen has beeutaken up, ltering ofi the catalyst and distilling off the residue or thesolvent in vacuo, and recrystallize ing the formed para-N-sec-alkylamino-phenol.

7 fl. The process of making,peiso-propylaminophenol comprising the solution of p-(isopropylidene-amino) phenol alcohol, adding platinum oxide as a catalyst, shaking the :mixture in an atmosphere oi hydrogen until the required amount ofhydrogen has been takenup, filtering off the catalyst'and distilling 01f the residue of alcohol in 'vacuo, and recrystallizing the formed paraiso-proplyamino-phenol from benzene. -5. In the process of making p-isopropyl-amino phenol, from p-amino phenol, the step of intermediately forming p-(isopropylideneamino)-- phenol by condensation with acetone. 7 I

6; In the process of making para-N-sec-alkylaminophenols with the chemical formula p-RRCHNHCpH4OI-I, in which;R and R are.alkyl radicals, the step of reducing the reaction product of p-aminophenol and an aliphatic ketone with the formula RR'CO in which R and R have the .connotation as above, by hydrogen with the aid of a metal hydrogenationcata'lyst.

' 7.'In. a, process of making para-N-sec-alkylaminophenols, with the formula of p-RR'- CHNHCeI-I OI-I, in which R and R arealkyl radicals, the' stepof reducingthe reaction product of paminophenol and an aliphatic ketone with the formula aa'c=o, by hydrogen and with the aid of platinum as a catalyst. f i

8. In a process of making para-N-sec-alkylamino-phenols with the formulap-RR'CHNHCa- 'HiOH, in which R and R are alkyl radicals, from p-amino-phenol, the step of intermediately forming a i p- (isoalkylidene-amino) -pheno1 with the formula, RR C=N C6II4OH, by condensation of the p aminophenol with an aliphatic ke'tone with the formula RRCO.

' RANDOLPH T. MAJOR.

.of the p-amino phenol 

